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Biomedical subjects

O Svendsen

Publications and source records attributed to O Svendsen.

At least 19 recordsLinked to original sources
PubMed1992

Effect of immunosuppressive agents on the guanethidine-induced sympathectomy in athymic and euthymic rats.

Guanethidine sulphate causes destruction of peripheral sympathetic neurons and infiltration of mononuclear inflammatory cells in the sympathetic ganglia of both athymic nude (rnu/rnu) and euthymic LEW/Mol rats. The effect of guanethidine is believed to be an autoimmune reaction. To determine the effect of immunosuppressive drugs concurrently with guanethidine treatment both athymic and euthymic rats were treated with guanethidine 40 mg/kg i.p. daily for 14 days, cyclophosphamide 100 mg/kg i.p. on days 1 and 8, methylprednisolone 10 mg/kg and cyclosporin A 10 mg/kg daily from days 1 to 7, and then every other day from days 8 to 14. The number of neurons in the sympathetic ganglia was counted and four subpopulations of mononuclear inflammatory cells were identified by monoclonal antibodies MHC II, CD8 T-cells/NK-cells, CD5 T-cells, CD4 T-cells/macrophages. Our results show that the immunosuppressive drugs used were unable to prevent the guanethidine-induced reduction of sympathetic neurons, although the number, of neurons following guanethidine-methylprednisolone treatment was significantly higher compared with guanethidine alone in both athymic and euthymic rats. The identification of mononuclear cells in the sympathetic ganglia showed that the CD8/NK and CD5 populations were the populations primarily responding to guanethidine treatment. Both CD8/NK and CD5 populations were absent without guanethidine, but increased significantly following guanethidine in both athymic and euthymic animals. None of the immunosuppressive drugs used could prevent the guanethidine-induced rise in the CD8/NK population in neither athymic nor in euthymic rats. The rise in the CD5 population was suppressed following treatment with all immunosuppressive drugs in athymic rats, but only following methylprednisolone in euthymic animals. These results indicate that guanethidine induces proliferation of T-cells in euthymic rats and non-functional CD5 positive pre T-cells in athymic animals. The CD5 population in both athymic and euthymic animals appears relatively more sensitive to immunosuppressive drugs than the NK-cell population also activated by guanethidine. This relatively resistant NK-cell population seems to play an important role in the guanethidine-induced destruction of sympathetic neurons and can explain why the guanethidine-induced immunological reaction could not be fully prevented by the immunosuppressive drugs used. The conclusion is that guanethidine induces destruction of sympathetic neurons by a NK-cell-mediated reaction.

Animals↗
PubMed1992

Athymic experimental animals in pharmaco-immunological research.

Immunodeficient animals--the nude mouse and the nude rat--allow studies of drug action and possible side effects without interference from the immune system. Comparative investigations in athymic and euthymic animals allowed us to elucidate the role of T-lymphocytes in the pathogenesis of streptozotocin-induced diabetes mellitus in mice, and the importance of NK-cells as effectors in guanethidine-induced sympathectomy in the rat. It is suggested that immunodeficient animals should be included in toxicological studies of xenobiotics.

Animals↗
PubMed1992

Anti-asialo GM1 antibodies prevents guanethidine-induced sympathectomy in athymic rats.

Guanethidine sulphate induces destruction of peripheral sympathetic neurons and infiltration of mononuclear cells in rat sympathetic ganglia. The effect of guanethidine is believed to be an autoimmune reaction. In order to determine the effect of anti-asialo GM1, an antibody that binds to the glycolipid asialo GM1 expressed on rodent natural killer cells, athymic Lewis rats received guanethidine 40 mg/kg i.p. daily from day 1 to 14 and anti-asialo GM1 i.p. 1 mg/rat on day -2, 0, 2, 6, and 10 in the study period. Saline and anti-asialo GM1 were given alone in the same doses as control. The number of neurons in the sympathetic ganglia were counted and the ganglionic volume determined. The presence of natural killer cells in the ganglia were determined by immunohistochemical methods. Our results shows that anti-asialo GM1 can prevent guanethidine-induced reduction of sympathetic neurons, but not prevent the initiation of an immunological reaction in the ganglia. Natural killer cells could only be identified in ganglia following guanethidine treatment alone. It is concluded that anti-asialo GM1 treatment can prevent the guanethidine-induced sympathectomy by eliminating the natural killer cells from the ganglia.

Animals↗
PubMed1992

Rederivation of rat colonies seropositive for Bacillus piliformis and the subsequent screening for antibodies.

Latent infection of rats in a breeding colony with Bacillus piliformis detectable by antibodies to the agent in an immunofluorescence assay was eliminated by a combination of traditional rederivation techniques, using animal units not previously used for rat breeding, and the use of specific disinfection procedures. The success rate was apparently correlated with the use of peracetic acid instead of aldehyde products to decontaminate the animal unit.

Animal Husbandry↗
PubMed1991

Pretreatment with steroids before intravenous injection of diatrizoate or iohexol. Effects on urine and serum profiles.

The effects on urine and serum profiles of intravenous injection of diatrizoate, iohexol, or saline were studied in male rats pretreated with steroids or saline. Using urinary albumin, glucose, sodium, and the enzymes lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), and N-acetyl-beta-D-glucosaminidase (NAG) as markers of glomerular and tubular function, it was found that diatrizoate caused temporary glomerular and tubular dysfunction; the effect was independent of the kind of pretreatment. Iohexol did not cause increased glomerular permeability in steroid- and saline-pretreated rats. When used following saline, iohexol induced increased excretion of three tubular components, whereas iohexol plus steroids caused increased excretion of all five tubular components. The dysfunctional effect of iohexol plus steroids was less than that of diatrizoate plus steroids. The serum components revealed no abnormalities induced by either contrast media or methylprednisolone. Pretreatment with steroids has no effect on the glomerular or tubular dysfunctional effect of diatrizoate, whereas it worsens the temporary tubular dysfunctional effect of iohexol in rats.

Acetylglucosaminidase↗
PubMed1991

Effect of human growth hormone on the reproduction of female rats.

Female rats were treated with human growth hormone (hGH) 0.3, 1.0 and 3.3 IU/kg daily for two weeks before mating, throughout mating and during the first seven days of pregnancy. Treatment with 1.0 and 3.3 IU/kg hGH caused a significant prolongation of the oestrous cycle. As a consequence the number of mating days was more than doubled compared to placebo treatment. The number of implantation sites and corpora lutea was significantly higher in hGH treated rats than in placebo treated rats. The number of early resorptions was increased in the rats given 3.3 IU/kg. The number of foetuses in rats sacrificed on day 20 of pregnancy and the number of viable offspring from the rats allowed to give birth were significantly increased by treatment with 1.0 IU/kg hGH. In a study of 4-day cyclic rats, treatment with 3.3 IU/kg hGH caused a prolongation of the cycle length to an average of 10.1 days, and the plasma progesterone levels tended to be higher in those rats in which the cyclic patterns had been most deranged. Foetal body weights were increased in the hGH groups, and a study with 125I-hGH indicated that hGH administered to pregnant rats will to some extent pass the placenta.

Animals↗
PubMed1991

Muscle toxicity of diatrizoate and iohexol in rabbits. A model for local tissue damage.

The potential tissue irritating effect of diatrizoate and iohexol was studied by injecting the contrast media into the right longissimus dorsi muscle of rabbits. The left muscle served as control. The animals were sacrificed 3 days after the injection, at which time muscle tissue was examined for macroscopic changes and loss of the muscle enzyme creatine kinase (CK) from the injection site was determined. An irregular area of necrotic muscle tissue and a hemorrhage was found at the injection site in rabbits given diatrizoate, whereas iohexol only caused hemorrhage. The local loss of CK activity following diatrizoate (0.64 g muscle tissue) was statistically significantly greater than following iohexol (0.18 g muscle tissue). It is concluded that this model seems to be useful for identification of the irritating potential of contrast media. It is also concluded that diatrizoate caused more damage to the local muscle tissue than iohexol.

Animals↗
PubMed1990

Identification of the mononuclear cell infiltrate in the superior cervical ganglion of athymic nude and euthymic rats after guanethidine-induced sympathectomy.

Guanethidine sulphate 40 mg/kg intraperitoneally for 14 days induced chromatolysis and nerve cell death in the superior cervical ganglia of athymic nude (rnu/rnu) LEW/Mol rats and their euthymic (+/rnu) LEW/Mol heterozygous littermates. Histologically the sympathetic ganglia were dominated by an infiltration of small inflammatory cells. By means of monoclonal antibodies these cells were identified. The number of B-lymphocytes increased following guanethidine in both athymic and euthymic rats. The number of T-lymphocytes increased to a great extent in euthymic rats, but was virtually missing in athymic rats. The number of NK-cells and monocytes/macrophages increased in both athymic and euthymic rats. The conclusion is, that guanethidine exerts a direct effect on sympathetic ganglion cells followed by a thymus-independent immune response.

Animals↗
PubMed1990

Epidemiological studies of Bacillus piliformis infection and Tyzzer's disease in laboratory rats.

Characteristics in connection with the presence of Bacillus piliformis in the barrier-protected animal rooms of a breeding centre for laboratory rats are discussed. The incidence of antibodies against B. piliformis in IFA test is high -77.8% for the total breeding centre. Clinical and pathological changes are, however, rare and mainly connected with certain rat strains. Immunosuppression with prednisolone and subsequent histopathological tests of liver sections indicate that rats with MHC-type RT1.A-u have an increased risk of developing Tyzzer's disease, while RT1.A-1-carriers seem to be resistant to this disease.

Animals↗
PubMed1979

Long term effect of teflutixol on apomorphine-induced stereotypy and vomiting in dogs.

Dose--response relationships to apomorphine-induced vomiting and stereotyped running behaviour have been determined in dogs before, and up to 24 and 28 days respectively, after daily oral treatment with 2.5 mg/kg of teflutixol or 12 days. The ED50 values for apomorphine-induced vomiting after teflutixol were not different from those obtained before treatment. Stereotyped running behaviour of increasing intensity was seen 4--12 days after teflutixol treatment. The intensity then declined and returned to normal. The results suggest that the nigro-neostriatal dopamine system in dogs became hypersensitive after prolonged teflutixol treatment, while the dopamine receptors of the emetic chemotrigger zone did not.

Animals↗
PubMed1979

The loss of creatine phosphokinase (CK) from intramuscular injection sites in rabbits. A predictive tool for local toxicity.

The CK activity was measured in muscle tissue taken from the injected area (dorsal longissimus muscle) and the contralateral side of the injection site 72 hours after intramuscular injection into rabbits of 1 ml of different dilutions of propylene glycol or glycerol formal in distilled water or 0.9% saline. The total loss of CK activity from the injection site was calculated as the difference between the CK concentration in the normal muscle tissue and that of the injection site from the same animal. From the results the arbitrary amount of muscle tissue depleted of CK activity was further calculated and compared with the severity of the gross pathological findings. A large necrotic area at the injection site was present in all samples with more than 1 g of muscle tissue depleted of CK activity. Minor and probably acceptable pathological changes were found in samples with less than 1 g of muscle tissue depleted of CK activity. The local damaging effect of drug preparations for intramuscular use can thus be evaluated from the calculated amount of muscle tissue depleted of CK activity.

Animals↗
PubMed1978

Hepatotoxicity of citalopram in rats and first-pass metabolism.

A chronic oral toxicity study of citalopram in rats revealed dose dependent hepatic fatty infiltrations in male rats while female rats were unaffected. Subsequent studies demonstrated markedly reduced availability due to first-pass hepatic metabolism in male rats and roughly complete availability in females. Pretreatment of male rats with phenobarbital for 2 weeks caused increased metabolism and simultaneous administration of phenobarbital and citalopram gave more pronounced fatty infiltrations than citalopram alone. A connection is suggested between the first-pass metabolism in male rats and the hepatotoxicity, which is possibly mediated through a metabolite or intermediate formed in toxic amount during the first passage of the liver.

Administration, Oral↗
PubMed1978

A comparative study of serum creatine phosphokinase (CPK) activity in rabbits, pigs and humans after intramuscular injection of local damaging drugs.

Serum creatine phosphokinase (CPK) activity has been determined before and after intramuscular injection of lidocaine, diazepam or saline in humans and lidocaine, diazepam, digoxin and saline in pigs and rabbits. Two ml volum of each of the drugs was given to humans as well as to the experimental animals. No changes in CPK activity were found after saline in humans or rabbits but a minor increase was demonstrated in pigs. A marked increase of CPK activity was demonstrated after lidocaine or diazepam in humans and after lidocaine, diazepam or digoxin in pigs and rabbits. Post mortem examination of the injection sites in the animals revealed extensive muscle tissue necrosis after lidocaine, diazepam and digoxin. No damage of the tissue was found after saline. CPK activity was also determined in rabbits receiving 2 ml of dilutions of diazepam in saline. The injection sites were examined post mortem. The CPK activity was increased in animals receiving 1:2 and 1:8 dilutions while a 1:20 dilution did not give rise to changes in the enzyme activity. The necrotic area diminished when diazepam was diluted and no pathological changes were found at the injection sites after the 1:20 dilution. Measuring the CPK activity in rabbits after an intramuscular injection seems to be a sensitive method for the determination of local toxicity.

Animals↗
PubMed1978

Studies on Tyzzer's disease in rats.

An outbreak of an epidemic disease occurred in a specified-pathogen-free (SPF) breeding colony of rats. The clinical signs and the post-mortem findings were characteristic for Tyzzer's disease. The causative agent, Bacillus piliformis, was demonstrated microscopically in ileum, liver and myocardium, and transmitted to mice where its pathogenicity appeared to be similar to that of another strain isolated from mice. B. piliformis from spontaneously-infected rats was demonstrated by indirect immunofluorescence technique. By means of the same technique it was found that the fluorescence antibody titre obtained of the individual sera from spontaneously-infected mice, rats and rabbits was the same, whether the antigen employed was organisms isolated from rats or mice. By testing sera from healthy rats in 3 different colonies by use of immunofluorescence technique, antibodies were found in several sera.

Animals↗
PubMed1977

Pharmacology of a new phthalane (Lu 10-171), with specific 5-HT uptake inhibiting properties.

The pharmacological profile of a new bicyclic substance, Lu 10-171 (1-(3-(dimethylamino)propyl)-1-(p-fluorophenyl)-5-phthalancarbonitril), is described and compared with that of existing tricyclic thymoleptics. In mice and rats the compound exhibited marked 5-HT potentiating properties both in vivo and in vitro, being 5-10 times as active as chlorimipramine. The tests included 5-HT-, 5-HTP- and tryptophan-potentiation. In monoamine oxidase inhibitor treated dogs and rabbits the compound caused a marked hyperthermia. In rabbits this effect was completely blocked by pretreatment with the tryptophan hydroxylase inhibitor, p-chlorophenylalanine. Hyperthermia induced by the central catecholamine displacing substance H 77/77 in rats was not affected by Lu 10-171, whereas the substance abolished the temperature rise induced by H 75/12. Reserpine- and tetrabenazine-induced ptosis and tetrabenazine-induced immobility in mice were antagonized by relatively low doses of existing tricyclic thymoleptics, whereas Lu 10-171 was very weak in this respect. Very weak in vitro anticholinergic and antihistaminergic properties were also registered for Lu 10-171. It is concluded that Lu 10-171 is a very potent and highly specific potentiator of 5-HT both in vivo and in vitro probably due to inhibition of 5-HT uptake. Thus this compound might be a useful agent in studying the role of 5-HT neurone systems in the control of mood. The substance does not possess the NA potentiating and anticholinergic and antihistaminergic properties characteristic of the tricyclic antidepressants.

5-Hydroxytryptophan↗